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Physiology

Cardiac Output:

Minute Volume = Heart Rate X Stroke Volume

Heart rate, HR at rest = 65 to 85 bpm  

Each heartbeat at rest takes about .8 sec. of which .4 sec. is quiescent period.

Stroke volume, SV at rest = 60 to 70 ml.

Heart can increase both rate and volume with exercise. Rate increase is limited due to necessity of minimum ventricular diastolic period for filling. Upper limit is usually put at about 220 bpm. Maximum heart rate calculations are usually below 200. Target heart rates for anaerobic threshold are about 85 to 95% of maximum.

Terms:

End Diastolic Volume, EDV - the maximum volume of the ventricles achieved at the end of ventricular diastole. This is the amount of blood the heart has available to pump. If this volume increases the cardiac output increases in a healthy heart.

End Systolic Volume, ESV - the minimum volume remaining in the ventricle after its systole. If this volume increases it means less blood has been pumped and the cardiac output is less.

EDV - ESV = SV

SV / EDV = Ejection Fraction The ejection fraction is normally around 50% at rest and will increase during strenuous exercise in a healthy heart. Well trained athletes may have ejection fractions approaching 70% in the most strenuous exercise.

Isovolumetric Contraction Phase - a brief period at the beginning of ventricular systole when all valves are closed and ventricular volume remains constant. Pressure has risen enough in the ventricle to close the AV valves but not enough to open the semilunar valves and cause ejection of blood. 

Isovolumetric Relaxation Phase - a brief period at the beginning of ventricular diastole when all valves are closed and ventricular volume is constant. Pressure in the ventricle has lowered producing closure of the semilunar valves but not opening the AV valves to begin pulling blood into the ventricle.

Dicrotic Notch - the small increase in pressure of the aorta or other artery seen when recording a pulse wave. This occurs as blood is briefly pulled back toward the ventricle at the beginning of diastole thus closing the semilunar valves.

Preload - This is the pressure at the end of ventricular diastole, at the beginning of ventricular systole. It is proportional to the End Diastolic Volume (EDV), i.e. as the EDV increases so does the preload of the heart. Factors which increase the preload are: increased total blood volume, increased venous tone and venous return, increased atrial contraction, and the skeletal muscular pump.

Afterload - This is the impedence against which the left ventricle must eject blood, and it is roughly proportional to the End Systolic Volume (ESV). When the peripheral resistance increases so does the ESV and the afterload of the heart. 

The importance of these parameters are as a measure of efficiency of the heart, which increases as the difference between preload and afterload increases

Conductivity :

 Means ability of cardiac muscle to propagate electrical impulses through the entire heart ( from one part of the heart to another)  by the excitatory -conductive system of the heart.
 
Excitatory conductive system of the heart involves:


1. Sinoatrial node ( SA node) : Here the initial impulses start and then conducted to the atria through  the anterior inter-atrial pathway ( to the left atrium) , to the atrial muscle mass through the gap junction, and to the Atrioventricular node ( AV node ) through anterior, middle , and posterior inter-nodal pathways.
The average conductive velocity in the atria is 1m/s.

2- AV node : The electrical impulses can not be conducted directly from the atria to the ventricles , because of the  fibrous skeleton , which is an electrical isolator , located between the atria and ventricles. So the only conductive way is the AV node . But there is a delay in the conduction occurs in the AV node .
This delay is due to:
- the smaller size of the nodal fiber.
- The less negative resting membrane potential
- fewer gap junctions.

There are three sites for delay:
- In the transitional fibers , that connect inter-nodal pathways with the AV node ( 0.03 ) .
- AV node itself ( 0.09 s) .
- In the penetrating portion of Bundle of Hiss ( 0.04 s)  .
This delay actually allows atria to empty blood in ventricles during the cardiac cycle before the beginning of ventricular contraction  , as it prevents the ventricles from the pathological high atrial rhythm.
The average velocity of conduction in the AV node is 0.02-0.05 m/s

3- Bundle of Hiss : A continuous with the AV node that passes to the ventricles through the inter-ventricular septum. It is subdivided into : Right and left bundle. The left bundle is also subdivided into two branches: anterior and posterior branches .


4- Purkinje`s fibers: large fibers with velocity of conduction 1.5-4 m/s.
the high velocity of these fibers is due to the abundant gap junctions , and to their nature as very large fibers as well.
The conduction from AV node is a one-way conduction . This prevents the re-entry of cardiac impulses from the ventricles to the atria.
Lastly: The conduction through the ventricular fibers has a velocity of 0.3-0.5 m/s.

Factors , affecting conductivity ( dromotropism)  :

I. Positive dromotropic factors :

1. Sympathetic stimulation : it accelerates conduction and decrease AV delay .
2. Mild warming
3. mild hyperkalemia
4. mild ischemia
5. alkalosis

II. Negative dromotropic factors :

1. Parasympathetic stimulation
2. severe warming
3. cooling
4. Severe hyperkalemia
5. hypokalemia
6. Severe ischemia
7. acidosis
8. digitalis drugs.

The pancreas

The pancreas consists of clusters if endocrine cells (the islets of Langerhans) and exocrine cells whose secretions drain into the duodenum.

Pancreatic fluid contains:

  • sodium bicarbonate (NaHCO3). This neutralizes the acidity of the fluid arriving from the stomach raising its pH to about 8.
  • pancreatic amylase. This enzyme hydrolyzes starch into a mixture of maltose and glucose.
  • pancreatic lipase. The enzyme hydrolyzes ingested fats into a mixture of fatty acids and monoglycerides. Its action is enhanced by the detergent effect of bile.
  • 4 zymogens— proteins that are precursors to active proteases. These are immediately converted into the active proteolytic enzymes:
    • trypsin. Trypsin cleaves peptide bonds on the C-terminal side of arginines and lysines.
    • chymotrypsin. Chymotrypsin cuts on the C-terminal side of tyrosine, phenylalanine, and tryptophan residues (the same bonds as pepsin, whose action ceases when the NaHCO3 raises the pH of the intestinal contents).
    • elastase. Elastase cuts peptide bonds next to small, uncharged side chains such as those of alanine and serine.
    • carboxypeptidase. This enzyme removes, one by one, the amino acids at the C-terminal of peptides.
  • nucleases. These hydrolyze ingested nucleic acids (RNA and DNA) into their component nucleotides.

The secretion of pancreatic fluid is controlled by two hormones:

  • secretin, which mainly affects the release of sodium bicarbonate, and
  • cholecystokinin (CCK), which stimulates the release of the digestive enzymes.

Vital Capacity: The vital capacity (VC) is the maximum volume which can be ventilated in a single breath. VC= IRV+TV+ERV. VC varies with gender, age, and body build. Measuring VC gives a device for diagnosis of respiratory disorder, and a benchmark for judging the effectiveness of treatment. (4600 ml)

Vital Capacity is reduced in restrictive disorders, but not in disorders which are purely obstructive.

The FEV1 is the % of the vital capacity which is expelled in the first second. It should be at least 75%. The FEV1 is reduced in obstructive disorders.

Both VC and the FEV1 are reduced in disorders which are both restrictive and obstructive

Oxygen is present at nearly 21% of ambient air. Multiplying .21 times 760 mmHg (standard pressure at sea level) yields a pO2 of about 160. Carbon dioxide is .04% of air and its partial pressure, pCO2, is .3.

With alveolar air having a pO2 of 104 and a pCO2 of 40. So oxygen diffuses into the alveoli from inspired air and carbon dioxide diffuses from the alveoli into air which will be expired. This causes the levels of oxygen and carbon dioxide to be intermediate in expired air when compared to inspired air and alveolar air. Some oxygen has been lost to the alveolus, lowering its level to 120, carbon dioxide has been gained from the alveolus raising its level to 27.

Likewise a concentration gradient causes oxygen to diffuse into the blood from the alveoli and carbon dioxide to leave the blood. This produces the levels seen in oxygenated blood in the body. When this blood reaches the systemic tissues the reverse process occurs restoring levels seen in deoxygenated blood.

SPECIAL SOMATIC AFFERENT (SSA) PATHWAYS

Hearing

The organ of Corti with its sound-sensitive hair cells and basilar membrane are important parts of the sound transducing system for hearing. Mechanical vibrations of the basilar membrane generate membrane potentials in the hair cells which produce impulse patterns in the cochlear portion of the vestibulocochlear nerve (VIII)

Special somatic nerve fibers of cranial nerve VIII relay impulses from the sound receptors (hair cells) in the cochlear nuclei of the brainstem

These are bipolar neurons with cell bodies located in the spiral ganglia of the cochlea.

Vestibular System

The vestibulocochlear nerve serves two quite different functions.

The cochlear portion, conducts sound information to the brain,

The vestibular portion conducts proprioceptive information.

It is the central neural pathways

Special somatic afferent fibers from the hair cells of the macula utriculi and macula sacculi conduct information into the vestibular nuclei on the ipsilateral side of the pons and medulla.

These are bipolar neurons with cell bodies located in the vestibular ganglion.

 Some of the fibers project directly into the ipsilateral cerebellum to terminate in the uvula, flocculus, and nodulus, but most enter the vestibular nuclei and synapse there.

Vision

The visual system receptors are the rods and cones of the retina.

Special somatic afferent fibers of the optic nerve (II) conduct visual signals into the brain

Fibers from the lateral (temporal) retina of either eye terminate in the lateral geniculate body on the same side of the brain as that eye.

SSA II fibers from the medial (nasal) retina of each eye cross over in the optic chiasm to terminate in the contralateral lateral geniculate body.

Area 17 is the primary visual area, which receives initial visual signals.

Neurons from this area project into the adjacent occipital cortex (areas 18 and 19) which is known as the secondary visual area. It is here that the visual signal is fully evaluated.

The visual reflex pathway involving the pupillary light reflex - in which the pupils constrict when a light is shined into the eyes and dilate when the light is removed.

Some SSA II fibers leave the optic tract before reaching the lateral geniculates, terminating in the superior colliculi instead.

From here, short neurons project to the Edinger­Westphal nucleus (an accessory nucleus of III) in the midbrain, which serves as the origin of the preganglionic parasympathetic fibers of the oculomotor nerve (GVE III).

The GVE III fibers in turn project to the ciliary ganglia, from which arise the postganglionic fibers to the sphincter muscles of the iris, which constrict the pupils.

Regulation of Blood Pressure by Hormones

The Kidney

One of the functions of the kidney is to monitor blood pressure and take corrective action if it should drop. The kidney does this by secreting the proteolytic enzyme renin.

  • Renin acts on angiotensinogen, a plasma peptide, splitting off a fragment containing 10 amino acids called angiotensin I.
  • angiotensin I is cleaved by a peptidase secreted by blood vessels called angiotensin converting enzyme (ACE) — producing  angiotensin II, which contains 8 amino acids.
  • angiotensin II
    • constricts the walls of arterioles closing down capillary beds;
    • stimulates the proximal tubules in the kidney to reabsorb sodium ions;
    • stimulates the adrenal cortex to release aldosterone. Aldosterone causes the kidneys to reclaim still more sodium and thus water.
    • increases the strength of the heartbeat;
    • stimulates the pituitary to release the antidiuretic hormone (ADH, also known as arginine vasopressin).

All of these actions, which are mediated by its binding to G-protein-coupled receptors on the target cells, lead to an increase in blood pressure.

The Adrenal Glands

The adrenal glands are two small structures situated one at top each kidney. Both in anatomy and in function, they consist of two distinct regions:

  • an outer layer, the adrenal cortex, which surrounds
  • the adrenal medulla.

The Adrenal Cortex

cells of the adrenal cortex secrete a variety of steroid hormones.

  • glucocorticoids (e.g., cortisol)
  • mineralocorticoids (e.g., aldosterone)
  • androgens (e.g., testosterone)
  • Production of all three classes is triggered by the secretion of ACTH from the anterior lobe of the pituitary.

Glucocorticoids

They Effect by raising the level of blood sugar (glucose). One way they do this is by stimulating gluconeogenesis in the liver: the conversion of fat and protein into intermediate metabolites that are ultimately converted into glucose.

The most abundant glucocorticoid is cortisol (also called hydrocortisone).

Cortisol and the other glucocorticoids also have a potent anti-inflammatory effect on the body. They depress the immune response, especially cell-mediated immune responses. 

Mineralocorticoids

The most important of them is the steroid aldosterone. Aldosterone acts on the kidney promoting the reabsorption of sodium ions (Na+) into the blood. Water follows the salt and this helps maintain normal blood pressure.

Aldosterone also

  • acts on sweat glands to reduce the loss of sodium in perspiration;
  • acts on taste cells to increase the sensitivity of the taste buds to sources of sodium.

The secretion of aldosterone is stimulated by:

  • a drop in the level of sodium ions in the blood;
  • a rise in the level of potassium ions in the blood;
  • angiotensin II
  • ACTH (as is that of cortisol)

Androgens

The adrenal cortex secretes precursors to androgens such as testosterone.

Excessive production of adrenal androgens can cause premature puberty in young boys.

In females, the adrenal cortex is a major source of androgens. Their hypersecretion may produce a masculine pattern of body hair and cessation of menstruation.

Addison's Disease: Hyposecretion of the adrenal cortices

Addison's disease has many causes, such as

  • destruction of the adrenal glands by infection;
  • their destruction by an autoimmune attack;
  • an inherited mutation in the ACTH receptor on adrenal cells.

Cushing's Syndrome: Excessive levels of glucocorticoids

In Cushing's syndrome, the level of adrenal hormones, especially of the glucocorticoids, is too high.It can be caused by:

  • excessive production of ACTH by the anterior lobe of the pituitary;
  • excessive production of adrenal hormones themselves (e.g., because of a tumor), or (quite commonly)
  • as a result of glucocorticoid therapy for some other disorder such as
    • rheumatoid arthritis or
    • preventing the rejection of an organ transplant.

The Adrenal Medulla

The adrenal medulla consists of masses of neurons that are part of the sympathetic branch of the autonomic nervous system. Instead of releasing their neurotransmitters at a synapse, these neurons release them into the blood. Thus, although part of the nervous system, the adrenal medulla functions as an endocrine gland.The adrenal medulla releases:

  • adrenaline (also called epinephrine) and
  • noradrenaline (also called norepinephrine)

Both are derived from the amino acid tyrosine.

Release of adrenaline and noradrenaline is triggered by nervous stimulation in response to physical or mental stress. The hormones bind to adrenergic receptors  transmembrane proteins in the plasma membrane of many cell types.

Some of the effects are:

  • increase in the rate and strength of the heartbeat resulting in increased blood pressure;
  • blood shunted from the skin and viscera to the skeletal muscles, coronary arteries, liver, and brain;
  • rise in blood sugar;
  • increased metabolic rate;
  • bronchi dilate;
  • pupils dilate;
  • hair stands on end (gooseflesh in humans);
  • clotting time of the blood is reduced;
  • increased ACTH secretion from the anterior lobe of the pituitary.

All of these effects prepare the body to take immediate and vigorous action.

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